Renal glomerular atrial natriuretic factor receptors in one-kidney, one clip rats

One-kidney, one clip (1K1C) hypertension is often associated with an expanded plasma volume and (once the arterial clip is removed) with natriuresis. Blood pressure (BP), atrial and plasma concentrations of atrial natriuretic factor (ANF), hematocrit, and renal glomerular ANF receptors were therefore studied in 1K1C rats and in their normotensive uninephrectomized controls before and after unclipping. Six hours after removal of the clip, BP was normal in the 1K1C group and plasma ANF presented a sharp decline but was still significantly higher than in the normotensive controls, with a slight difference being evident 24 hours after unclipping. Hematocrit was lower in the 1K1C rats than in their control counterparts, but this difference tended to disappear once the clip was removed, indicating a contraction of plasma volume in these unclipped 1K1C animals. The renal glomerular ANF receptor population was markedly smaller in 1K1C rats than in the uninephrectomized controls but showed a twofold increase in number and affinity 24 hours after unclipping. It is concluded that the up-regulation and enhanced affinity of glomerular ANF receptors (probably secondary to the decrease in plasma levels of ANF) may contribute to the natriuresis reported in hypertensive 1K1C animals on removal of the arterial clip.     

Effects of chronically administered atrial natriuretic factor in aldosterone-infused hypertensive rats

To assess the pathophysiological role of atrial natriuretic factors in mineralocorticoid hypertension, we studied the effects of chronic infusion of synthetic atrial natriuretic factor on blood pressure and sodium-water excretion in rats with aldosterone salt-induced hypertension. Administration of synthetic atrial natriuretic factor (150 micrograms/kg/day) to rats made hypertensive by 7-day infusion of aldosterone (100 micrograms/kg/day) and sodium loading with 1% NaCl as drinking water returned the blood pressure to control levels, and the antihypertensive effect was not associated with any changes in urine volume and urinary sodium excretion. These results indicate that atrial natriuretic factors may be involved in the regulation of blood pressure in mineralocorticoid hypertension, independent of the renal effects of these substances.     

Impaired renorenal reflexes in two-kidney, one clip hypertensive rats

In normotensive rats, stimulation of renal mechanoreceptors by an increase in ureteral pressure results in a contralateral inhibitory renorenal reflex response with contralateral natriuresis. Similar effects are produced by stimulation of renal chemoreceptors by renal pelvic perfusion with 0.9 M NaCl. However, in spontaneously hypertensive rats the renorenal reflex responses to renal mechanoreceptor and chemoreceptor stimulation are impaired. The present study was performed to examine whether the renorenal reflexes were altered in two-kidney, one clip hypertensive rats, a model of hypertension in which it has been suggested that the afferent renal nerves contribute to the enhanced peripheral sympathetic nervous activity. A 0.2 mm silver clip was placed around one renal artery 4 weeks before the study. At the time of study, mean arterial pressure was 156 +/- 4 mm Hg. Renal mechanoreceptor and chemoreceptor stimulation of either the nonclipped or clipped kidney failed to affect ipsilateral afferent renal nerve activity, contralateral efferent renal nerve activity, and contralateral urine flow rate and urinary sodium excretion. Renal denervation of the nonclipped kidney increased ipsilateral urinary sodium excretion from 0.65 +/- 0.13 to 1.50 +/- 0.42 mumol/min/g and decreased contralateral urinary sodium excretion from 0.18 +/- 0.03 to 0.13 +/- 0.03 mumol/min/g (p less than 0.05). Thus, denervation of the nonclipped kidney resulted in a similar contralateral excitatory renorenal reflex response as in normotensive rats. However, denervation of the clipped kidney increased both ipsilateral and contralateral urinary sodium excretion, from 0.14 +/- 0.04 to 0.27 +/- 0.5 mumol/min/g and from 1.29 +/- 0.33 to 2.09 +/- 0.59 mumol/min/g (p less than 0.01), respectively. Taken together these data suggest that the lack of inhibitory renorenal reflexes from the clipped kidney may enhance efferent sympathetic nervous activity and thereby contribute to the hypertension in two-kidney, one clip hypertensive rats.     

Vascular renin-angiotensin system in two-kidney, one clip hypertensive rats

The possible role of the renin-angiotensin system in the maintenance of hypertension in two-kidney, one clip hypertensive rats was studied. Plasma renin activity rose rapidly and markedly in association with the elevation of blood pressure and then decreased gradually, although blood pressure remained high. Renin activity in the lung, aorta, and mesenteric artery also increased with the development of hypertension and then decreased in a way similar to that of plasma renin activity at the chronic stage of hypertension. Plasma angiotensin converting enzyme activity did not change significantly until 16 weeks after unilateral renal artery clipping, whereas vascular angiotensin converting enzyme activity significantly increased at the chronic, but not the acute, stage of hypertension. In chronically renal hypertensive rats, 1-sarcosine, 8-isoleucine angiotensin II or enalapril, an angiotensin converting enzyme inhibitor, lowered the blood pressure and enalapril also lowered the angiotensin converting enzyme activity of vascular tissues. The constrictor effect of angiotensin I was greater in isolated arteries from chronically hypertensive rats than in those from age-matched normotensive rats. These results suggest that the vascular renin-angiotensin system plays an important role in the maintenance of two-kidney, one clip hypertension. Elevated vascular angiotensin converting enzyme activity appears to increase local production of angiotensin II, which results in vasoconstriction by acting directly and indirectly through adrenergic nerves on vascular smooth muscle.     

Effect of DOCA-salt on angiotensin dependency and surgical reversal of hypertension in two-kidney, one clip renal hypertensive rats

The development of hypertension in two-kidney, one clip renal hypertensive rats (2K, 1C RHR) was not altered by treatment with DOCA and saline solution as drinking fluid for two months of observation. However, the administration of DOCA and salt suppressed plasma renin activity (PRA), the renal renin content (RRC) of the clipped kidney and the response to a single oral dose of captopril (10 mg/kg). The weight of the contralateral kidney was increased by the administration of DOCA-salt, while that of the ischaemic kidney was not changed. The withdrawal of DOCA-salt treatment restored the PRA and the effects of captopril to a similar degree to the non-treated group. The acute hypotensive effects of captopril were reduced on the 10th week compared with the 7th week after renal arterial constriction in 2K, 1C RHR. The fall in blood pressure induced by captopril significantly correlated with the initial PRA both in the 7th and 10th week after clipping. There was a significant correlation between PRA and RRC of the clipped kidney. Rats previously treated with DOC-salt had either removal of the contralateral kidney with removal of the clip from the ischaemic kidney, or removal of the ischaemic kidney. Blood pressure fell to normal levels in the unclipped group and in the nephrectomy group, but the fall in the latter group was transient and within two weeks had risen to significantly higher levels than in the unclipped group. It is concluded that structural vascular change following DOC-salt hypertension is insufficient to cause persisting hypertension except when it occurs in the renal circulation.     

Renal atrial peptide receptors and natriuresis in two-kidney, one clip hypertension.

It has been suggested that the impaired natriuretic response of the clipped kidney in two-kidney, one clip hypertensive rats is related to downregulation of renal atrial natriuretic peptide receptors. To test this hypothesis, blood volume expansion and atrial peptide binding studies were performed in this model. Infusion of 1% and then 1.5% body weight donor blood (n = 6) caused a progressive increase in plasma immunoreactive atrial natriuretic peptide (107 +/- 26 to 168 +/- 31 to 427 +/- 154 pg/ml, p less than 0.001); the sodium excretion of the nonclipped kidney rose from 230 to 2,200 to 4,000 neq/min (p less than 0.01) but that of the clipped kidney did not rise significantly. There was a highly significant correlation between log cyclic guanosine monophosphate and log sodium excretion by the nonclipped (r2 = 0.749) but not the clipped (r2 = 0.046) kidney. Between clipped and nonclipped kidneys, the association constant (5.26 +/- 0.89 versus 5.17 +/- 0.64 x 10(9)/mol) and apparent binding site density (575 +/- 92 versus 500 +/- 74 fmol/mg protein) for atrial peptide binding in isolated glomeruli did not differ. Assay of atrial peptide-induced cyclic guanosine monophosphate release by isolated glomeruli showed that clipped and nonclipped kidneys were equally responsive. Binding affinity and receptor density did not differ in homogenates prepared from inner medullas of clipped and nonclipped kidneys. These results show that the blunted natriuretic response in clipped kidneys was not associated with any relative decrease in number or function of glomerular or papillary atrial natriuretic peptide receptors.     

Atrial natriuretic factor: specific binding to renal glomeruli during the development of two-kidney, one clip hypertension in the rat

Blood pressure (BP), atrial and plasma concentrations of atrial natriuretic factor (ANF), hematocrit and renal glomerular ANF receptors were studied during the development of hypertension in two-kidney, one clip (2-K, 1C) rats and were compared with normotensive controls. Plasma ANF was elevated in the 2-K, 1C group in all stages of hypertension, even after 3 weeks when BP, although higher than in sham-operated animals, had not yet reached arbitrarily-set hypertensive levels. At this time, hematocrit was higher in the hypertensive rats than in the controls, but the difference later disappeared. Lower atrial ANF concentrations were observed in the 2-K, 1C group at week 3, but only in the right atrium. No difference in ANF levels was noted in either the left or right atrium between hypertensive and normotensive animals 5 and 7 weeks after clipping. The glomerular ANF receptor population was markedly smaller in the clipped left kidney of 2-K, 1C rats during all stages of hypertension, and in the untouched right kidney at 5 and 7 weeks after surgery, but was larger in the non-clipped right kidney in the pre-hypertensive phase (3 weeks). It is concluded that receptor density changes during the evolution of high BP in the 2-K, 1C Goldblatt model of experimental hypertension. Our data suggest that the increases and decreases in density of renal glomerular ANF receptors may play a role in the differential handling of sodium by the clipped and non-clipped kidney during the various stages of development of 2-K, 1C hypertension in the rat.     

In vivo left ventricular anatomy in rats with two-kidney, one clip and one-kidney, one clip renovascular hypertension.

OBJECTIVES: To evaluate differences in left ventricular structural changes related to different hemodynamic patterns. DESIGN: One-kidney, one clip (1K1C; volume-dependent hypertension) rats were two-kidney, one clip (2K1C; high-resistance hypertension) to determine whether these two types of Goldblatt rats showed different types of left ventricular adaptation. METHODS: M-mode echocardiography was used to study 28 2K1C and 19 1K1C Wistar rats 8 weeks after surgery and 55 age-matched control animals. RESULTS: Systolic blood pressure was equally high in the two models; the 1K1C rats had a larger left ventricular chamber and normal plasma renin activity (PRA), whereas in the 2K1C rats PRA was increased and the left ventricular chamber was normal. The atrial natriuretic factor was significantly increased only in the 2K1C rats and was related to PRA. The left ventricular mass index was increased in both models, but more in the 1K1C than the 2K1C rats. CONCLUSIONS: In both models the degree of left ventricular hypertrophy was associated with the interacting effects of the hemodynamic component superimposed on the primary hemodynamic pattern (i.e. blood pressure as an expression of pressure overload in the primarily volume-dependent 1K1C rats and the left ventricular chamber size as an expression of volume overload in the high-resistance 2K1C rats). The interaction between pressure and volume increased the left ventricular wall thickness in both models, with additional chamber enlargement in the 1K1C rats. In these rats, the increase in left ventricular mass was more pronounced due to the greater volume load on the heart.     

Distributions of microvascular pressure in skeletal muscle of one-kidney, one clip, two-kidney, one clip, and deoxycorticosterone-salt hypertensive rats

Studies were performed on the cremaster skeletal muscle in rats to investigate the microvascular changes that are associated with established one-kidney, one clip (1K1C) and two-kidney, one clip (2K1C) Goldblatt hypertension and with deoxycorticosterone (DOC)-salt hypertension. Rats were anesthetized with urethane and chloralose; and cremaster muscles with intact circulation and innervation were suspended in a controlled Krebs bath. Microvascular pressures and vessel diameters were measured at three consecutive arteriolar (A) and venular (V) branch levels. Arteriolar diameters (means +/- SEM) in normotensive (NT) rats were 119 +/- 7, 86 +/- 5, and 31 +/- 3 micron respectively for 1A, 2A, and 3A arterioles; and venule diameters were 218 +/- 12, 141 +/- 15, and 53 +/- 7 micron respectively for 1V, 2V, and 3V venules. As compared to NT rats, there was a selective decrease in lumen size (percent reduction from control) for 1A and 2A (23% to 38%) in 1K1C and 2K1C rats and for 1A, 2A, and 3A (42% to 44%) in DOC rats. Venule diameters were not significantly different between normotensive and hypertensive animals at any branch level. Femoral artery pressures were significantly elevated (greater than or equal to 43%) in all three forms of hypertension; however, this increase in pressure was not proportionally transmitted throughout the microcirculation. This was evidenced by normal pressure in 3A arterioles and in all venules for 1K1C and 2K1C rats and by normal pressures in 3V and larger venules for DOC rats. Our findings indicate that elevated arterial pressure in chronic renal hypertension is not transmitted uniformly across all microvascular segments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of angiotensin inhibition and renal denervation in two-kidney, one clip hypertensive rats

Neural and angiotensin-mediated influences that alter hemodynamic and excretory behavior of the nonclipped kidney of two-kidney, one clip hypertensive rats were assessed by sequential acute surgical denervation of the nonclipped kidney and intravenous infusion of converting enzyme inhibitor (SQ 20881), 3 mg/kg X hr. Normal and two-kidney, one clip hypertensive rats (0.2-mm silver clip on the right renal artery 3-4 weeks before study) were prepared to allow study of each kidney. Mean arterial blood pressure of two-kidney, one clip hypertensive rats fell significantly from control values of 149 +/- 6 to 135 +/- 6 mm Hg after denervation of the nonclipped kidney. Despite this decrease in arterial pressure, the nonclipped kidney exhibited significant increases in glomerular filtration rate (from 1.00 +/- 0.08 to 1.24 +/- 0.08 ml/min), sodium excretion (from 88 +/- 39 to 777 +/- 207 nEq/min), fractional sodium excretion (from 0.06 +/- 0.02 to 0.54 +/- 0.14%), and urine flow rate (from 3.7 +/- 0.5 to 8.2 +/- 1.1 microliter/min). A significant decrease in glomerular filtration rate (from 1.12 +/- 0.07 to 0.85 +/- 0.08 ml/min) with no change in excretory function was observed for the clipped kidney following denervation of the nonclipped kidney. Intravenous addition of converting enzyme inhibitor significantly increased renal blood flow (from 7.0 +/- 1.3 to 10.6 +/- 1.5 ml/min) and sodium excretion (from 777 +/- 207 to 1384 +/- 425 nEq/min) for the nonclipped kidney; blood pressure decreased from 135 +/- 6 to 123 +/- 4 mm Hg, and renal vascular resistance decreased significantly (from 22 +/- 3 to 13 +/- 2 mm Hg X min/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic captopril infusion in two-kidney, one clip rats with normal plasma renin concentration

Immediately after clipping, plasma renin and angiotensin II concentrations are raised in the two-kidney, one clip rat. Plasma renin and angiotensin II fall to relatively low levels between two and five weeks after operation, while blood pressure continues to rise. An experiment was carried out to determine whether complete suppression of angiotensin II during this two- to five-week period would have any effect on the development of hypertension. Captopril infused chronically (2 mg/kg/h) for up to 20 days completely prevented the rise in mean blood pressure [110.8 +/- 17.9 at day 0 compared to 88.3 +/- 8.4 (s.d.) mmHg at day 20] seen in an equivalent control group infused with dextrose (109.2 +/- 11.6 at day 0 compared to 131.7 +/- 23.6 mmHg at day 20). Preinfusion values for plasma renin and angiotensin II concentration were within the upper half of the range found for sham-operated normal rats. These findings would suggest that while the plasma levels of angiotensin II are low in relation to those seen immediately after clipping, they are still raised in comparison with normal sham-operated rats; this may contribute to the development of hypertension by a slow chronic, rather than an acute, effect.     

Vascular neuroeffector function in two-kidney, one clip hypertensive dogs

In control dogs and those made hypertensive for 1 and 8 months by partially occluding a renal artery, contractile responses of mesenteric artery strips to adrenergic nerve stimulation and to norepinephrine, plasma renin activity and vascular angiotensin converting enzyme (ACE) activity were compared. Contractile responses to norepinephrine were potentiated in the artery strips from 8-month-hypertensive dogs; however, the response to electrical stimulation of adrenergic nerves was not influenced. Contractions induced by the nerve stimulation were potentiated by a low concentration (2 X 10(-10) mol/l) of angiotensin (ANG) II; the potentiating effect was enhanced in 8-month-hypertensive dog arteries. 3H-overflow evoked by adrenergic nerve stimulation was increased by ANG II to a greater extent in superfused mesenteric artery strips obtained from hypertensive (8-month) dogs, previously soaked in 3H-norepinephrine. Angiotensin converting enzyme activity was markedly greater in 8-month-hypertensive dog mesenteric arteries than in normotensive dog arteries. It may be concluded that the hypertension is maintained by increased sensitivity of post-synaptic alpha 1-adrenoceptors and pre-synaptic ANG receptors and increased vascular ACE activity, possibly promoting the production of ANG II in the vascular wall.     

Unclipping of two-kidney, one clip hypertensive rats produces endothelium-dependent inhibition of sympathetic vasoconstriction

Removal of the renal artery-constricting clip in two-kidney, one clip (2-K,1C) Goldblatt-hypertensive rats produces a rapid fall in blood pressure which has been attributed to the release of vasodepressor lipids from the renal medulla. The aim of this study was to demonstrate the effect of unclipping 2-K,1C hypertensive rats, and of any hormone thereby released, on vasoconstrictor responses to sympathetic stimulation in the ex vivo blood-perfused tail artery, as well as the role of the vascular endothelium in mediating this effect. Blood was withdrawn at a rate of 2 ml/min from the carotid artery of an anaesthetized 2-K,1C rat and used to perfuse, via an extracorporeal circuit, a cannulated segment of tail artery which had been taken from a killed, normal rat and mounted in an organ bath. The blood was returned to the 2-K,1C rat via the jugular vein. Vasoconstriction and increases in perfusion pressure were produced by periarterial electrical stimulation of the tail artery. The tail artery was either intact or had had its endothelium removed. Sham operations which did not remove the renal artery clip did not change blood pressure or vasoconstrictor responses. Unclipping lowered blood pressure and reduced vasoconstrictor responses in ex vivo blood-perfused tail arteries in which the endothelium was intact, but did not decrease responses in tail arteries from which the endothelium had been removed. It is concluded that unclipping releases a hormone which lowers blood pressure and inhibits sympathetic vasoconstrictor responses via an endothelium-dependent mechanism.     

Regional myocyte size in two-kidney, one clip renal hypertension

Regional variations in the size and shape of isolated myocytes were studied using the two-kidney, one clip (2K1C) renal model of hypertension. Weanling male Sprague-Dawley rats (50 to 75 g) were anesthetized by ketamine (100 mg/kg) during renal artery clipping (0.2 mm internal diameter silver clip) and were then allowed to grow for 6 to 8 weeks, when the blood pressure had stabilized at 180 mmHg. Hearts were removed, weighed and then were perfused with a calcium-free Joklik medium containing collagenase. Isolated myocytes were collected from five regions and fixed in isoosmolar glutaraldehyde: right ventricular free wall (RVFW), right and left halves of the interventricular septum (RIVS, LIVS), and epicardial and endocardial halves of the left ventricular free wall (LEPI, LENDO). Myocyte volume was measured by Coulter Counter. Myocyte length was measured by sonic digitizer. Cross-sectional area was calculated from myocyte volume and length. Tailcuff systolic pressure and heart weight were significantly increased in 2K1C rats as compared to control. Body weights were not different. Cell volume was significantly increased in RIVS, LIVS, LEPI, and LENDO, but not in RVFW. Cell length was not significantly increased in any region. Thus, the 2K1C model showed a predominant left ventricular hypertrophy in which the right half of the septum acted in concert with the left ventricle. The shape of the hypertrophied myocytes, having an increase in volume due to an increase in cross-sectional area but not length, was most consistent with a pressure-induced form of cardiac hypertrophy.     

Angiotensin and angiotensin converting enzyme tissue levels in two-kidney, one clip hypertensive rats.

Renal tissue angiotensin I (Ang I) and II (Ang II) content and angiotensin converting enzyme activity were assessed in both kidneys during initial (7 days) and maintenance (25 days) phases of two-kidney, one clip hypertension in rats. At 7 and 25 days, systolic arterial pressure was 146 +/- 2 and 170 +/- 7 mm Hg, respectively. After 7 days, Ang I content of clipped kidneys was 64% and 70% higher (p < 0.001) than in nonclipped and sham-operated kidneys, respectively, when compared with levels in kidneys from sham-operated rats. In kidneys harvested 25 days after clipping one renal artery, Ang I and Ang II contents in clipped kidneys were increased 102% and 24% (p < 0.01), respectively. Ang II content was also 32% higher in nonclipped kidneys. Angiotensin converting enzyme activity in nonclipped kidneys was greater (p < 0.05) than that in either clipped (46% higher) or sham-operated kidneys (57% higher). Plasma Ang I and Ang II levels were elevated at 7 days but were not different at 25 days in clipped rats. These results demonstrate a dissociation between intrarenal and circulating levels of Ang I and Ang II and suggest that qualitatively different mechanisms may be responsible for the elevated intrarenal Ang II levels during the initial and maintenance phases of renal hypertension.     

Synthesis of catecholamines in the hypothalamus and brainstem in one-kidney, one clip and two-kidney, one clip hypertension in rabbits

In order to examine the role of central catecholaminergic neurons in hypertension, the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines, was studied in the hypothalamus, midbrain, pons-upper medulla, mid-medulla and lower medulla of one-kidney, one clip (1-K,1C) and two-kidney, one clip (2-K,1C) hypertensive rabbits and their respective operated controls (1-K,1 Cc and 2-K,1 Cc). Comparing the 1-K,1 C group to the 1-K, 1 Cc group, the activity of TH was increased by 79% in the hypothalamus (P less than 0.02), 37% in the mid-medulla region (P less than 0.02) and was unchanged in the midbrain, pons-upper medulla and the lower medulla. Comparing the 2-K,1 C group to the 2-K,1 Cc group, the activity of TH was increased by 89% in the mid-medulla (P less than 0.01), decreased by 36% in the pons-upper medulla (P less than 0.01) and unchanged in the hypothalamus, midbrain and lower medulla. These results indicate that similarities and differences exist in the contribution of central catecholaminergic neurons to the pathophysiology of 1-K,1 C and 2-K,1 C hypertension in rabbits.     

Central and peripheral catecholamine synthesizing enzymes during the development of two-kidney, one clip hypertension in rats

The activities of the catecholamine synthesizing enzymes have been determined in discrete brain areas and in peripheral tissues of rats, at different times after clipping the left renal artery (two-kidney Goldblatt hypertension, 2KGH) and in sham operated animals. Three days after clipping the only enzymatic change was a slight decrease in plasma dopamine-beta-hydroxylase (DBH) activity. Ten days after clipping no change in enzymatic activity was found at the central level. However, the DBH and the phenylethanolamine-N-methyltransferase (PNMT) activities were increased in the adrenal medulla (+49.0%, P less than 0.001 and +36.6%, P less than 0.001, respectively) and DBH activity was also increased in the superior cervical ganglia (+22.8%, P less than 0.01). These data suggest that sympathetic hyperactivity is present in 2KGH rats when hypertension is established. In addition, as this type of hypertension does not alter the PNMT activity in brainstem areas, it seems that the alterations in PNMT activity reported for genetically hypertensive rats are unlikely to be secondary to the elevated blood pressure.     

Antihypertensive effect of synthetic atrial natriuretic factor in vasopressin-infused rats

To assess the pathophysiological role of atrial natriuretic factors in the regulation of blood pressure, we studied the effect of chronic infusion of a synthetic atrial natriuretic factor of 25 amino-acid residues on blood pressure and sodium-water excretion. Experimental subjects were rats with hypertension made by chronic infusion of vasopressin on regular intakes of sodium or on sodium loading with 1% NaCl as drinking water. When a subdepressor dose (150 micrograms/kg/day) of synthetic atrial natriuretic factor was delivered via an osmotic minipump into the jugular vein simultaneously with 7.2 U/kg/day of vasopressin infused intraperitoneally by another osmotic minipump, the expected elevation of systolic blood pressure was completely inhibited. This was not accompanied by any changes in urine volume and urinary sodium excretion. The antihypertensive effect was sustained throughout the experimental period lasting 3 days in rats on regular sodium intake (p less than 0.01) or on sodium loading with 1% NaCl as drinking water (p less than 0.01). These results indicate that a subdepressor dose of synthetic atrial natriuretic factor can modulate the vasopressor effect of vasopressin. Therefore it is suggested that an atrial natriuretic factor may be involved in the regulation of blood pressure via its antagonizing effect to vasopressin.